Mitochondrial DNA (mtDNA) in mammals is a closed circular molecule about 16.2 kilobases in length. It consists of a variety of genes including thirteen peptides that serve in electron transport and oxidative phosphorylation. Recently the importance of defective mtDNA in several human disorders has been recognized. Consequently, knowledge of basic molecular genetics of mammalian mtDNA is of fundamental importance. The proposed research focuses on the types of mutations and mutation rates that occur in mammalian mtDNA. The research also will elucidate factors that constrain or otherwise affect mutation rate and the rate(s) at which mtDNA evolves. Finally, one aspect of the proposed research involves comparative analysis of some of the peptides and the genes that encode the peptides. The research takes an evolutionary perspective because evolutionary patterns can reveal many of the factors that have determined the characteristics of mtDNA. Continued funding is requested to further test the hypothesis that gene rearrangements have occurred in at least one group of mammals, Neotropical fruit bats of the genus Artibeus. Two other hypotheses also will be tested: 1) that respiratory peptides in bats have diverged from those in other mammals; and 2) that demography has affected the patterns of divergence seen in mtDNA in these animals. The use of bats as a model for learning more about mammalian mtDNA is partly based on the discovery that mtDNA appears to evolve very rapidly in these animals and that their mtDNA exhibits an unexpected pattern in the types of base pair substitutions (transversions vs. transitions) that occur. Furthermore, preliminary analyses of two peptides (ND1 and ND5) that form part of the NADH ubiquinone oxidoreductase complex has suggested that these peptides in bats differ from the same peptides in other kinds of mammals. This could be important because bats have very high energy requirements in comparison to other mammals.